HIV and TB in Sub-Saharan Africa: Learning from a Catastrophic Collision

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1 HIV and TB in Sub-Saharan Africa: Learning from a Catastrophic Collision Richard E. Chaisson, MD Center for Tuberculosis Research Johns Hopkins University

2 A global view of HIV infection A global view of HIV infection 38.6 million people [ million] living with HIV, 2006

3 Increasing HIV seroprevalence among pregnant women in selected areas of Africa: % seroprevalence Maputo (Mozambique ) Source: US Census Bureau/WHO KwaZulu-Natal (South Africa) Windoek (Namibia) Yaounde (Cameroon)

4 Impact of HIV on Life Expectancy in Africa Life expectancy 50 at birth (years) Botswana South Africa Swaziland Zambia Zimbabwe

5 Global Burden of Tuberculosis 2005 WHO Estimates All forms of TB Multidrug - resistant TB (MDR-TB) Estimated number of cases 8.8 million 424,000 Estimated number of deaths 1.6 million 116,000 extensively drug-resistant TB (XDR-TB) 27,000 16,000

6 Global TB Incidence Rates, No estimate < and more Stop TB Department

7 Rising TB incidence in HIV+ gold miners in South Africa Rates per 100,000 per year HIV+ HIV- Corbett EL et al AIDS 2000;14:

8 Effect of ART on Risk of TB in HIV+ Patients in the Khayelitsha Cohort Time to next TB episode, pre-art and on-art 2 month lag before entering analysis Pre-ART ART Surival free of subsequent TB diagnsosis ART Pre-ART Logrank p< Months since enrolment or on ART Cox HR for ART vs pre-art = 0.41 ( ) Logrank p< Months since enrolment or on ART n Failed Survival 72 (69-74) 53 (49-57) 39 (34-44) 77 (73-80) 56 (51-60) 43 (36-49) n Failed Survival 85 (82-87) 76 (72-79) 68 (61-73) 90 (87-92) 80 (76-84) 72 (65-78) Boulle et al., 9th International workshop in HIV Observational Databases Budapest, April 2005

9 TB is the Most Common Opportunistic Infection in Patients Starting HAART Setting TB Incidence in 90 d after HAART Developing Countries Developed Countries 25.5/100 person years 3/100 person years M. Egger, CROI 2007

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11 A New Scourge: Extensively Drug Resistant TB (XDR) XDR TB Multidrug resistant TB (MDR TB) is TB resistant to key first line drugs for treating TB (INH/rifampin) Extensively drug resistant TB (XDR TB) is MDR TB that is also resistant to 2-3 of the second line drugs for TB (fluoroquinolones, injectables ) An epidemic of XDR TB has been detected in Kwa Zulu Natal, South Africa, among HIV+ patients

12 XDR TB in KwaZulu-Natal, South Africa, Reports of high TB mortality in pilot HIV treatment program in Tugela Ferry, rural KZN, in 2005 Cross-sectional study of TB suspects attending rural hospital 1539 TB suspects, 544 (35%) diagnosed with TB by culture 221/544 (41%) with MDR TB 53/221 (24%, 10% of total) with XDR TB 26 (49%) had no prior TB treatment 44 tested for HIV, all infected 52 (98%) died; 15 were on ARVs Median survival = 16 days XDR TB now documented in 28 health care institutions throughout KNZ, ~350 cases Gandhi et al., Lancet 2006; 368: ; WHO 2007

13 Survival of Patients with XDR TB in Tugela Ferry, Kwa-Zulu Natal, South Africa Proportion Surviving Days since Sputum Collected Gandhi et al., Lancet 2006; 368:

14 XDR TB: Back to the Magic Mountain? How widespread is XDR TB? What needs to be done to contain it? Can TB be controlled in an era of XDR?

15 HIV leading infectious cause of death TB 2 nd leading infectious cause of death 3.0 Millions of deaths in HIV/AIDS Tuberculosis Malaria Measles WHO 2005

16 Global Control of TB and of HIV Tales of Failure with Some Rays of Hope What does the HIV response have that TB could benefit from? What does the TB response have that HIV could benefit from? How can HIV and TB control efforts work together to conquer both diseases?

17 Strengths of the HIV Response (and what TB is lacking) Advocacy and commitment Money PEPFAR: $15 billion $30 billion Global Fund for ATM Emphasis on individual needs and rights A big pipeline of new drugs, diagnostics and preventatives Willingness to innovate

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20 NIH Infectious Disease Spending FY05 Actual (dollars in millions) 3,500 3,000 2,921 2,500 2,000 1,500 1, HIV/AIDS STDs/Herpes Smallpox Anthrax Influenza Tuberculosis Pneumonia Hepatitis C Malaria Courtesy of Mark Harrington, Treatment Action Campaign

21 NIH Investment: TB vs. HIV (2005) 3000 $ Millions Total Basic Science Drugs Vaccines TB HIV Courtesy of Mark Harrington, Treatment Action Campaign

22 People in sub-saharan Africa on antiretroviral treatment as percentage of those in need, Source: WHO/UNAIDS (2005). Progress on global access to HIV antiretroviral therapy: An update on 3 by

23 Strengths of the TB Response (and what HIV is lacking) Public health approach with strong monitoring and evaluation Emphasis on community needs and rights Cheap drugs that can cure and prevent disease A plan to control the disease STOP-TB Partnership global buy-in Epidemiologically based Regional subplans Timelines, benchmarks, budgets!

24 Stopping TB Now The Stop TB Partnership

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26 Total available funding and funding gaps for implementation,

27 Key Financial Aspects of the Global Plan 80% of needs are for country-level activities $44.3 billion 40% of country activities are for Africa $19.4 billion Total gap is $31 billion, $11 billion for Africa TB/HIV gap is $3 billion

28 Planned achievements: Incidence

29 TB Strategies That Could Be Applied to HIV Care Adherence support DOT for ART (DOT-HAART) Contact evaluations for patients who test HIV+ or for those starting HAART Registries and surveillance for incidence and outcomes of therapy A Global Plan that would control HIV with country benchmarks, timelines and budgets

30 HIV Strategies That Could Be Applied to TB Care Resources and Research Presidential TB Initiative? Improved diagnostic tools Culture for smear-negative and extrapulmonary TB Drug susceptibility testing Better drugs, with vigorous drugdevelopment program Individualized regimens, especially for drugresistant TB

31 Bringing Science to TB Control What Technological Advances Could Improve TB Control? New TB diagnostics Point of care tests, e.g., dipsticks New TB drugs Drugs to shorten treatment Drugs for MDR and XDR TB Drugs that can be given with ARVs New TB vaccines A vaccine that actually works!

32 Bringing Epidemiology to TB Control What Public Health Strategies Could Improve TB Control? TB diagnostics Make better use of existing technology Active case finding to identify prevalent cases TB drugs Use drugs that we know work, e.g., rifampin Use TB preventive therapy Infection control Prevent TB transmission in clinics and hospitals

33 Bringing HIV and TB Programs Together HIV testing of TB patients In Africa, 50+% of TB patients have HIV Screening for TB in HIV patients 3% of HIV+ pregnant women have active TB 8% of HIV VCT clients have active TB TB preventive therapy for HIV patients Preventive therapy works but isn t used

34 Progress of the Global Plan to Stop TB ( ) Activity 2006 Target 2005 Achievement HIV Testing of TB patients TB screening of HIV patients INH preventive therapy for HIV patients 1.6 million 14% 11 million 1.7% 1.2 million 2% WHO 2007

35 C R E A E Mission To organize, implement and evaluate novel public health strategies to reduce tuberculosis incidence in populations with high rates of HIV and TB co-infection. Funded by the Bill and Melinda Gates Foundation

36 The CREATE Portfolio of Population Level Studies Study/Site Intervention(s) Design (N) Thibela TB SA Gold Mines ZAMSTAR Zambia/South Africa THRio Rio de Janeiro Mass TB preventive therapy Intensive TB case finding, household interventions Preventive therapy and ARVs Cluster randomized trial (~60,000) Community randomized trial (~1 million) Phased implementation trial (15,000)

37 Thibela TB Study Preventing TB in Miners

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39 Community sputum collection depot School drama on TB in Western Cape, SA

40 Risk of TB in Brazilian HIV Patients by ART and INH Treatment Status Golub et al., AIDS 2007 Exposure category Person- Years TB Cases Incidence Rate (per 100 PYs) Incidence Rate Ratio No Rx 3, ( ) 1.0 ART only 11, ( ) 0.48 ( ) IPT only ( ) 0.32 ( ) Both 1, ( ) 0.20 ( ) Total 17, ( )

41 TB & HIV FIND TB Undiagnosed TB is common in PLWHIV TREAT TB Early treatment saves lives Treatment reduces transmission Prevent TB Isoniazid preventive therapy (IPT) works

42 Implications for the World Bank TB remains neglected, under-funded and continues to ravage Africa, especially in PLWHIV Investment in TB services, integrated HIV/TB care programs and community level interventions urgently needed Operational research to improve the impact of new and existing services important Advocacy for changes in policy and practice required if scale up of TB interventions is to succeed

43 Gates Foundation Press Briefing on TB and HIV at the Bangkok AIDS Conference July 15, 2004 The world has made defeating AIDS a top priority. This is a blessing. But TB remains ignored. Today we are calling on the world to recognize that we can t fight AIDS unless we do much more to fight TB as well. -Nelson Mandela